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Lifelong tissue memory relies on spatially organized dedicated progenitors located distally from the injury [scRNAseq_gradient]

ABSTRACT: Lifelong tissue memory relies on spatially organized dedicated progenitors located distally from the injury [scRNAseq_gradient]

PROVIDER: PRJNA914254 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22827600_1.fastq.gz	Fastqsanger.gz
	SRR22827600_2.fastq.gz	Fastqsanger.gz
	SRR22827700_1.fastq.gz	Fastqsanger.gz
	SRR22827700_2.fastq.gz	Fastqsanger.gz
	SRR22827800_1.fastq.gz	Fastqsanger.gz

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Lifelong tissue memory relies on spatially organized dedicated progenitors located distally from the injury [bulkRNAseq]

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Lifelong tissue memory relies on spatially organized dedicated progenitors located distally from the injury [ATAC-Seq]

Project description:Lifelong tissue memory relies on spatially organized dedicated progenitors located distally from the injury [ATAC-Seq]

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Lifelong tissue memory relies on spatially organized dedicated progenitors located distally from the injury [bulkRNAseq]

Project description:It is believed epithelial cells that have participated in a wound repair elicit a more efficient but locally restricted response to future injuries. However here we show that the cell adaptation resulting from a localised tissue damage has a wide spatial impact at a scale not previously noticed. We demonstrate that away from injured site, after a first injury a specific epithelial stem cell population gives rise to long term wound-memory progenitors residing in their own niche of origin. Notably these progenitors have not taken part in the first wound healing but become pre-activated through priming. This adaptation differs from classical features of trained immunity previously shown to be adopted by other epithelial stem cells. Our newly identified wound-distal memory cells display an intrinsic pre-activated state, maintained at chromatin and transcriptional level, leading to an enhanced wound repair ability that can be partially recapitulated through epigenetic perturbation even in absence of an injury. Importantly, the harmful consequences of wound repair, such as exacerbated tumorigenesis, occur within these primed cells and follow their spatial distribution. Overall, we show that sub-organ scale adaptation of an injury relies on spatially organized and memory-dedicated progenitors, characterized by a chromatin actionable cell state, that establishes an epigenetic field cancerization and predisposes to tumour onset.

2023-02-02 | GSE221403 | GEO

Lifelong tissue memory relies on spatially organized dedicated progenitors located distally from the injury [scRNAseq_gradient]

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Lifelong tissue memory relies on spatially organized dedicated progenitors located distally from the injury [ATAC-Seq]

2023-02-02 | GSE221408 | GEO

Pericentromeric heterochromatin is hierarchically organized and spatially contacts H3K9me2/3 islands located in genomic euchromatin

Project description:Pericentromeric heterochromatin is hierarchically organized and spatially contacts H3K9me2/3 islands located in genomic euchromatin

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Peroxisome function relies on organelle-associated mRNA translation

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Alzheimer's vulnerable brain region relies on a distinct retromer core dedicated to endosomal recycling.

Project description:Whether and how the pathogenic disruptions in endosomal trafficking observed in Alzheimer's disease (AD) are linked to its anatomical vulnerability remain unknown. Here, we began addressing these questions by showing that neurons are enriched with a second retromer core, organized around VPS26b, differentially dedicated to endosomal recycling. Next, by imaging mouse models, we show that the trans-entorhinal cortex, a region most vulnerable to AD, is most susceptible to VPS26b depletion-a finding validated by electrophysiology, immunocytochemistry, and behavior. VPS26b was then found enriched in the trans-entorhinal cortex of human brains, where both VPS26b and the retromer-related receptor SORL1 were found deficient in AD. Finally, by regulating glutamate receptor and SORL1 recycling, we show that VPS26b can mediate regionally selective synaptic dysfunction and SORL1 deficiency. Together with the trans-entorhinal's unique network properties, hypothesized to impose a heavy demand on endosomal recycling, these results suggest a general mechanism that can explain AD's regional vulnerability.

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Wnt signaling control by KDM5C during development impacts lifelong cognition

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Gene expression in organized and disorganized human breast epithelial cells

Project description:We have reported more than a dozen microenvironmental factors whose signaling must be integrated in order to effect an organized, functional tissue morphology. In order to identify underlying commonalities in gene transcription associated with the phenotype, we compared the gene expression of organized and disorganized epithelial cells of the HMT-3522 breast cancer progression series: the non-malignant S1 cells that form polarized spheres (‘acini’), the malignant T4-2 cells that form large tumor-like clusters, and the ‘phenotypically reverted’ T4-2 cells that polarize as a result of correction of the microenvironmental signaling. 24 samples were analyzed: 5 samples were non-malignant S1 cells that formed organized spherical structures ('acini'), 5 samples were the isogenic malignant counterpart of S1 cells, namely the T4-2 cells, which grow into disorganized large cell clusters; and 14 samples of T4-2 cells that had been treated with different reverting agents, these reverting agents cause the T4-2 cells to 'revert' in phenotype so that they resemble the structures formed by S1 cells.

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